The present invention relates to novel compositions of matter. More particularly, the present invention relates to 2-, 3-, or 4-pyridinylmethylamino arylic acids. These compounds are potent thromboxane A.sub.2 synthetase inhibitors and/or 5-lipoxygenase inhibitors and as such represent useful pharmacological agents.
Since the discovery that human platelets convert the prostaglandin endoperoxide (PGH.sub.2) into a labile proaggregatory molecule known as thromboxane A.sub.2 (TXA.sub.2), researchers have sought compounds that could selectively inhibit the biological activity of TXA.sub.2. This end may be achieved in two different ways: the synthesis of TXA.sub.2 can be blocked by inhibiting the TXA.sub.2 synthetase, or a compound could be a receptor level antagonist of TXA.sub.2. As therapeutic agents, TXA.sub.2 synthetase inhibitors are more useful. See, e.g., R. Gorman, "Biological and Pharmacological Evaluation of Thomboxane Synthetase Inhibitors," Advances in Prostaglandin and Thromboxane Research, 6:417 (1980), and references cited therein. Most important are compounds which selectively inhibit TXA.sub.2 synthetase. Id.
In mammalian metabolism, arachidonic acid is transformed to 12-L-hydroperoxy-5,8,10,14-eicosatetraenoic acid by the action of 12-lipoxygenase. See, Hamberg, et al, Proc. Nat. Acad. Sci. 71:3400-3404 (1974). Similarly, 5-lipoxygenase transforms arachidonic acid into 5-S-hydroperoxy-6,8,11,14-eicosatetraenoic acid. Thus, an agent which inhibits the action of lipoxygenase would be useful in treating or preventing untoward conditions associated with lipoxygenase products.